7-7969632-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138426.4(GLCCI1):​c.282C>A​(p.Ser94Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000067 in 1,015,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

GLCCI1
NM_138426.4 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10
Variant links:
Genes affected
GLCCI1 (HGNC:18713): (glucocorticoid induced 1) This gene encodes a protein of unknown function. Expression of this gene is induced by glucocorticoids and may be an early marker for glucocorticoid-induced apoptosis. Single nucleotide polymorphisms in this gene are associated with a decreased response to inhaled glucocorticoids in asthmatic patients. [provided by RefSeq, Feb 2012]
GLCCI1-DT (HGNC:40852): (GLCCI1 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18698618).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GLCCI1NM_138426.4 linkc.282C>A p.Ser94Arg missense_variant Exon 1 of 8 ENST00000223145.10 NP_612435.1 Q86VQ1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GLCCI1ENST00000223145.10 linkc.282C>A p.Ser94Arg missense_variant Exon 1 of 8 1 NM_138426.4 ENSP00000223145.5 Q86VQ1

Frequencies

GnomAD3 genomes
AF:
0.000341
AC:
50
AN:
146448
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00117
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000152
Gnomad OTH
AF:
0.000496
GnomAD4 exome
AF:
0.0000207
AC:
18
AN:
868500
Hom.:
0
Cov.:
33
AF XY:
0.0000195
AC XY:
8
AN XY:
410092
show subpopulations
Gnomad4 AFR exome
AF:
0.000432
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000761
Gnomad4 OTH exome
AF:
0.000139
GnomAD4 genome
AF:
0.000341
AC:
50
AN:
146556
Hom.:
0
Cov.:
31
AF XY:
0.000350
AC XY:
25
AN XY:
71338
show subpopulations
Gnomad4 AFR
AF:
0.00117
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000152
Gnomad4 OTH
AF:
0.000490
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000261

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 16, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.282C>A (p.S94R) alteration is located in exon 1 (coding exon 1) of the GLCCI1 gene. This alteration results from a C to A substitution at nucleotide position 282, causing the serine (S) at amino acid position 94 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.48
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.028
T
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.22
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.39
T
M_CAP
Pathogenic
0.36
D
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-0.47
N
REVEL
Benign
0.087
Sift
Benign
0.087
T
Sift4G
Benign
0.087
T
Polyphen
0.97
D
Vest4
0.24
MutPred
0.24
Loss of glycosylation at S94 (P = 0.0016);
MVP
0.39
MPC
0.62
ClinPred
0.64
D
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.043
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1053762973; hg19: chr7-8009263; API